It was found that all four CSFs, GM-CSF, G-CSF, M-CSF, and IL-3, can induce the production of IL-6 that does not induce the formation of colonies but can induce myeloid
precursor cells to differentiate (reviewed in refs. 26-29 and 40). In a colony with differentiated cells, induction of a colony by the CSFs is thus followed by production of another cytokine, IL-6, which can induce differentiation of different cell lineages.
This induction of a differentiation factor by a growth factor serves as an effective mechanism to couple growth and differentiation. The CSFs and IL-6 may also switch on other, so
far unidentified, cytokines that are required to determine the specificity of the final cell type. In addition, IL-6 and GM-CSF can positively autoregulate their own induction (41) and can
induce expression of other cytokines including M-CSF, GMCSF, IL-6, IL-lα, IL-1β, and TNF (42). There is thus a cytokine network which allows amplification of signals and
indirect activity of cytokines by inducing production of other cytokines.